Partitioning of cancer therapeutics in nuclear condensates.
Science
; 368(6497): 1386-1392, 2020 06 19.
Article
in En
| MEDLINE
| ID: mdl-32554597
ABSTRACT
The nucleus contains diverse phase-separated condensates that compartmentalize and concentrate biomolecules with distinct physicochemical properties. Here, we investigated whether condensates concentrate small-molecule cancer therapeutics such that their pharmacodynamic properties are altered. We found that antineoplastic drugs become concentrated in specific protein condensates in vitro and that this occurs through physicochemical properties independent of the drug target. This behavior was also observed in tumor cells, where drug partitioning influenced drug activity. Altering the properties of the condensate was found to affect the concentration and activity of drugs. These results suggest that selective partitioning and concentration of small molecules within condensates contributes to drug pharmacodynamics and that further understanding of this phenomenon may facilitate advances in disease therapy.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cell Nucleus
/
Drug Resistance, Neoplasm
/
Neoplasms
/
Antineoplastic Agents
Limits:
Humans
Language:
En
Journal:
Science
Year:
2020
Document type:
Article
Affiliation country:
Estados Unidos